Pathophysiology and Aging of Bone

Sources: http://www.springerlink.com/content/x208624555xgu576/

This is an article in regards to pathophysiology and aging of bone by Peitschmann et al.

I will list out the points of interest in this article.

Bone loss due to aging:

1) overall decline in protein synthesis and protein turnover and accumulation of damaged molecules
2) number of adhesion colony forming cells significantly lower in marrow cells
3) requirement of higher concentration of growth factors and hormones
==> Impaired growth of human endosteal bone cells from men aged over 50 years
4) lower production of osteocalcin after stimulation with 1,25-(OH)2D3

Age related osteopenia may result from inversely related changes in pool size of hematopoietic osteoclast precursor cells and osteogenic stromal cells; reduced production of osteoprotegerin and enhanced RANKL expression would additionally promote the formation of osteoclasts.

Currently available markers of bone formation are:
total and bone-specific alkaline phosphatase activity, osteocalcin and type I collagen terminal extension peptides.
Bone resorption is assessed by
urinary excretion or serum levels of bone type I collagen degradation products eg. pyridinium crosslink and N- and C-telopeptide of collagen crosslinks.

Factors affecting invidividual bone mass include:
A) Peak bone mass (the amount of bone mass achieved at skeletal maturity)
B) Subsequent rate of bone loss

What is bone quality, one may ask. According to Mary Bouxsein: "the totality of features and characteristics that influence a bone's ability to resist fractures". Nevertheless, compromised trabecular architecture portrays as an independent causal factor in the pathogenesis of vertebral fractures.

It is well established that estrogen deficiency is a major determinant of the accelerated bone loss in postmenopausal women. This leads to the most infamous term called "osteoporosis" which everyone in the world knows and aware about it. One of the major worry which medical personnals are concerned of is the fracture of the neck of the femur in osteoporotic patients. Of course there are other fractures that could happen in osteoporotic bone in this case, eg. Colles fracture and crush fractures of thoracic and lumbar verterbra. For short, osteoporosis contributes in the increment of fragility (low energy) fractures and severity of traumatic (high energy) fractures.

HORMONAL INFLUENCES IN BONE LOSS

Androgen deficiency can impale high-turnover osteopenia in males (be it rats or males). Unfortunately, there isn't a clear distinction in this statement as some studies quoted positive correlation between free androgen index and femoral neck bone mineral density. It is interesting to note that in the study conducted by Kelly and coworkers (1990) reported that radial bone mineral density could be predicted by an index of free testosterone and weight. However, the fact that bioavailable estrogen was most strongly associated with bone mineral density, and thus, bioavailable of estrodiol rather than testosteonr is used as the most consistent predictors of bone turnoever and bone loss. There is another possible role of using dehydroepiandrosterone (DHEA) and DHEA sulfate to correlate bone density in healthy women.

OTHER INFLUENCE

We know that growth hormones stimulate growth. Nevertheless it stimulates the growth of bones. It is not surprising to note that growth hormone secretion declines as we age. Role of growth hormone/insulin-like growth factor is clearly shown in cases with growth hormone deficiency, leading to dwarfism and acromegaly in cases of excess growth hormones. 1,25-dihydroxyvitamin D3 acts as a central regulator of calcium and phosphorus homeostasis. It is interesting to note that there exists an association between bone mineral density and vitamin D receptor allele. As shown in literatures, vitamin D receptor polymorphisms appear to influence bone mineral density in primary as well as secondary osteoporosis.

To summarize, estrogen deficiency acts as the major determinant of bone loss in women and men whilst Vit D3 portray as a factor of bone turnover in elderly.

RIGGS, KHOSLA AND MELTON UNITARY MODEL OF INVOLUTIONAL OSTEOPOROSIS

Involutional osteoporosis is defined as the common form of osteoporosis that begins in middle life and becomes increasingly more frequent with age and there are two tyesp: type I ("postmenopausal") and type II ("senile").
Type I osteoporosis presents during the first 15-20 years after menopause and is characterized by excessive loss of trabecular bone, which causes the fractures typical of postmenopausal osteoporosis such as vertebral fractures and Colles' fracures. Type II is characterized by loss of trabecular and cortical bone, and the most frquent fractures involve the proximal femur and vertebra.

One point of interesting note is that cigarette smoking has been identified as risk factor for low bone mineral density. It is shown that 25-OH vitamin D and osteocalcin levels are low in smokers. Impairment of intestinal calcium absorption may contribute to the bone loss as well.

To conclude, humans will get old, we can get old. Nevertheless, with the understanding of these conditions, it is possible that one can prevent osteoporosis by doing the right activities to minimize of one's risk of getting osteoporosis. So start a healthy diet, do exercise and stop smoking!!!